Treatment: what really works best?

Gus Cairns

Published: 03 February 2012

The
new edition of the HIV treatment guidelines from the British HIV Association
(BHIVA) is now out for public consultation. HTU editor Gus Cairns was one of
the two patient representatives on the writing panel, and says that this stands
to be the most authoritative set of guidelines yet.

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BHIVA, essentially, is the body that represents the opinions
and interests of HIV doctors and allied professionals in the UK. It doesn’t
have to represent patients but has gone out of its way to encourage them to
take positions of influence within the organisation. There is a patient
representative on its ruling Executive Committee (EC), who is an ex officio trustee; I was the
predecessor of the current EC representative, Silvia Petretti. BHIVA also has
four permanent sub-committees that each have a position for a patient rep, and
regularly appoints ad hoc working
groups, which include patient representatives, for specific jobs such as
writing sets of standards and guidelines. These are usually advertised on the
UK-CAB website (www.ukcab.net).

One job I’d avoided until now, though, was anything to do
with writing treatment guidelines. I knew from experience that there’s no point
in being a patient rep unless you do some hard work. I was worried that I would
have to spend hours wading through scientific studies evaluating evidence.

Although the actual work burden was not too bad, I wasn’t
wrong about the amount of evidence. This set of treatment guidelines will be
the first to be issued for three and a half years. They are normally issued
biennially, but this time round the process of gathering and reviewing evidence
had to pass an NHS accreditation process adopted in 2009 (see www.evidence.nhs.uk/accreditation).
That meant it had to be done in a much more rigorous way.

There’s no set global standard for the evidence upon which
guidelines are based. In theory they could simply be the opinion of a group of
experts sitting round a table. Expert opinion, however, is often fallible.
Doctors tend to base their opinions on their own patients, who may not be typical;
negative results and non-results are notoriously less likely to be published;
even people of integrity can be swayed by studies hyped by PR firms. What you
think you know ain’t always so.

For this reason, most guidelines attempt to ‘grade’
evidence. This means that you look at each piece of scientific evidence and
decide how reliable it is, and how crucial in health terms. It can be done by
strength of recommendation, and by reliability of scientific evidence. There
are three grades of scientific reliability. Grade 1, the best, is results from
randomised trials that pit one treatment against another or against placebo.
Grade 2 is data from cohort or population studies; these report what happens in
large groups of patients, but results may be distorted by causes that aren’t
captured by the data. Grade 3 is expert opinion and case reports. There are
also, in the case of the US
guidelines, three different strengths of recommendation, A, B and C for ‘strong’,
‘moderate’ and ‘optional’.

I'm trying in everything I do to represent the diversity of our community. Roy Trevelion, patient representative

So you could have a strong recommendation based on weak
evidence (A3). This might apply, say, where a potentially lethal side-effect
has been observed but where it’s difficult to say how common it is. Or you
could have an optional recommendation based on strong evidence (C1), as when a
rigorous scientific study establishes an outcome difference in something that
doesn’t crucially affect health, like a tendency to get headaches.

These grades are still fallible, however, to experts’
knowledge of trials and to their opinion of how important specific outcomes
are. So, for instance, one might regard a (statistically significant) 5%
superiority for treatment A over treatment B in terms of patients achieving an
undetectable viral load as clinching evidence in favour of treatment A. Another
expert, however, might regard the fact that, although only a small number of
patients drop dead from heart attacks, 20% more do on treatment A than B as an
ironclad reason to favour treatment B.

In some cases, billions of pounds may depend on the result
of such disputes, so there may be bitter battles over evidence. HIV is no
stranger to this, especially when the cost of drugs is involved. BHIVA was well
aware, for instance, of the decision by the London Specialist Commissioning
Group to recommend Kivexa
(abacavir/3TC) over Truvada (tenofovir/FTC)
as first-line therapy for patients with a viral load under 100,000 copies/ml.

BHIVA accordingly stepped up the calibre of its evidence
grading for the most crucial recommendations, to the point where the new
guidelines may be the most rigorously evaluated anywhere. Firstly, doctors
writing a particular section voted on how important they thought particular
outcomes were (viral undetectability, speed of viral suppression, side-effects,
CD4 count, resistance and so on). They then employed a health researcher to
comb through every piece of evidence pertaining to the most crucial outcomes
and generate what are called ‘forest plots’ – diagrams that show the overall
strength of evidence across the range of available studies. In this case, two
of the most crucial decisions – firstly, the choice of nucleoside drugs, which
involves for most patients the Kivexa/Truvada
decision, and secondly, the choice of which third drug to put alongside those –
the result was two documents, one of 52 pages and one of 146.

Some crucial recommendations

The results? BHIVA recommends Truvada over Kivexa, not
for particular patients, but generally. As for the third drug, it will broaden
the choice: those 146 pages found that there was a dead heat between efavirenz
(Sustiva, also in the combination
pill Atripla), raltegravir (Isentress), ritonavir-boosted atazanavir
(Reyataz) and ritonavir-boosted darunavir
(Prezista) in terms of efficacy, but
demoted lopinavir/ritonavir (Kaletra).

In terms of when to start treatment, BHIVA sticks to a CD4
count of 350 cells/mm3 as the starting threshold – already
having decided that the study that persuaded the US guidelines to suggest
500 cells/mm3 was probably influenced by healthcare conditions in
the US.4 However, it broadens
the range of patients recommended to start earlier. This includes - though is
not restricted to - patients with hepatitis B or untreated hepatitis C, and
patients with neurocognitive problems. And it suggests that older patients, who
are particularly prone to rapid CD4 count falls, should be considered for early
therapy.

This article is too short to contain the many other recommendations,
but they can all be read in the consultation document.

There are, however two other sections that people living
with HIV might be particularly interested in: the section on Supporting the Patient to take
Antiretroviral Therapy and the section on Treatment as Prevention. Although the EACS guidelines have a
section on patient readiness, the former is BHIVA’s first statement in
treatment guidelines of what doctors need to do in order to assist people and
evaluate whether they have the right support to benefit from therapy.

The latter, as far as I’m aware, is an innovation in any set
of HIV treatment guidelines. The US guidelines mention that
antiretroviral therapy lowers patients’ infectiousness, but makes no
recommendations on what to do about it, even though the guidelines include
safer-sex counselling recommendations. The current draft of the BHIVA guidelines
recommends that the fact that treatment with ART lowers the risk of
transmission “is discussed with all patients”, and that if, following
discussion, people at any CD4 count wish “to start ART to reduce the risk of
transmission to partners, this decision is respected and ART is started”.

Being involved

This may all sound like a lot of
work, but the individual burden wasn’t so bad. The guidelines writing group
included 32 people. Most were doctors skilled in their area, so in some topic
areas (how to combine HIV treatment with cancer chemotherapy, to give one
example) I was happy to review the documents but take them on trust.

Now, I’m aware that I may be regarded as expert in some
areas myself, so people may be thinking “Fine for Gus, but I’d never get
involved in something like that myself.” Don’t just take my word for it. The guidelines
were regarded as sufficiently important to need the input of more than one
patient rep and so Roy Trevelion became the second one. Roy was diagnosed over 20 years ago but until
three years ago worked as an art director for the BBC, and is a newcomer to HIV
treatment activism.

He says: “I’ve been getting to grips with this and am very
impressed with the whole process. I’ve read all the drafts and evidence
summaries, with a medical dictionary in hand. But I actually see my lack of
experience as an advantage: I think it’s important to have someone who reviews these
guidelines from an ‘unpractised’ point of view, even if this means sometimes
bringing up issues that aren’t easily placed in a set of clinical guidelines,
such as issues of social disadvantage.

“I’m trying in everything I do to represent the diversity of
our community and to include the fact that, because we are all living longer,
HIV patients will face increasingly complex combinations of chronic illnesses -
and resultant complications in treatment and in who treats them.”

There was also a meeting with other members of UK-CAB to get
wider community feedback and a larger one is planned with HIV voluntary-sector
organisations.

Dr Ian Williams, chair of this writing group, is also
pleased with the outcome. He says: “We’ve tried to evaluate outcomes across all
trials instead of some, and spend most time evaluating the outcomes of most
importance to patients. The fact that they’ve been evaluated with regard to NHS
accreditation means that it will be more difficult to criticise particular
recommendations.”

There will be arguments, he acknowledges, and the whole
point of issuing a draft for consultation is to allow arguments to be made for
recommendations to be changed. But he’s confident in the robustness of the
process that has led to BHIVA’s new treatment recommendations.

Issue 210: Winter 2012

This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap

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This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends
checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member
of your healthcare team for advice tailored to your situation.